Cytochrome c of eucaryotic species are homologous and contain invariant amino acides in some 20% of the amino acid sequence. Understanding of the reason on which these amino acids have been selected by nature would help to understand the important properties of this protein essential for cellular respiration. An approach to the study of this reason is to replace the individual invariant amino acids with other amino acids by chemical synthesis and examine the effect on the structure-function-dynamics. Two major problems are involved in synthesis of cytochrome c by the Merrifield solid phase method, first joining of two fragments to form apocytochrome c and second, stereochemically specific covalent attachment of heme to apocytochrome c. As described in the previous years, the second problem has been solved by finding and solubilizing cytochrome c synthetase from mitochondria. We are now concerned with the first. Corradin and Harbury have shown that heme fragment [65-Hse-lactone] (1-65) and apofragment (66-104) obtained by treatment with CNBr of horse cytochrome c can be rejoined if the heme is reduced to facilitate formation of the methionine 80-S-heme bond. Our previous studies have shown that heme fragment ferri or ferro (1-25)H and apocytochrome c form a productive complex. Since our studies described in another report have indicated that leucine 32, the methionine 80-S-heme iron bond and probably also tryptophan 59 are involved in coupled interactions to stablize their atomic coordinates, apofragments [65-Hse-lactone](1-65) and (66-104) may form an ordered complex through this coupling if ferro heme fragment (1-25) is present. The complex thus formed would in turn facilitate the reaction of the homoserine-lactone of apofragment [65-Hse-lactone](1-65) with the Alpha-NH2-group of apofragment (66-104) to form apocytochrome c [65-Hse](1-104). Indeed, we have attained this joining in 40% efficiency. The product formed a productive complex with heme fragment (1-25)-H.